JPS63210101A - Manufacture of ultrafine porous chitosan or chitin particle - Google Patents
Manufacture of ultrafine porous chitosan or chitin particleInfo
- Publication number
- JPS63210101A JPS63210101A JP62043998A JP4399887A JPS63210101A JP S63210101 A JPS63210101 A JP S63210101A JP 62043998 A JP62043998 A JP 62043998A JP 4399887 A JP4399887 A JP 4399887A JP S63210101 A JPS63210101 A JP S63210101A
- Authority
- JP
- Japan
- Prior art keywords
- chitosan
- ultrafine
- particles
- water
- solution
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Granted
Links
- 229920001661 Chitosan Polymers 0.000 title claims abstract description 51
- 238000004519 manufacturing process Methods 0.000 title claims description 9
- 239000002245 particle Substances 0.000 title abstract description 36
- 229920002101 Chitin Polymers 0.000 title abstract description 27
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims abstract description 26
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims abstract description 15
- 239000012298 atmosphere Substances 0.000 claims abstract description 15
- 230000002378 acidificating effect Effects 0.000 claims abstract description 13
- 239000011882 ultra-fine particle Substances 0.000 claims abstract description 12
- 230000003472 neutralizing effect Effects 0.000 claims abstract description 6
- 239000003495 polar organic solvent Substances 0.000 claims abstract description 4
- 239000000126 substance Substances 0.000 claims abstract description 4
- 239000007864 aqueous solution Substances 0.000 claims description 13
- 239000003637 basic solution Substances 0.000 claims description 12
- 239000000203 mixture Substances 0.000 claims description 11
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 claims description 6
- 238000005507 spraying Methods 0.000 claims description 6
- 238000001035 drying Methods 0.000 claims description 4
- 230000000397 acetylating effect Effects 0.000 claims description 2
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 abstract description 30
- WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 abstract description 15
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 abstract description 12
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 abstract description 9
- JXTHNDFMNIQAHM-UHFFFAOYSA-N dichloroacetic acid Chemical compound OC(=O)C(Cl)Cl JXTHNDFMNIQAHM-UHFFFAOYSA-N 0.000 abstract description 6
- 238000006640 acetylation reaction Methods 0.000 abstract description 4
- BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 abstract description 4
- 238000005406 washing Methods 0.000 abstract description 4
- 229960005215 dichloroacetic acid Drugs 0.000 abstract description 3
- 230000000694 effects Effects 0.000 abstract description 3
- OSWFIVFLDKOXQC-UHFFFAOYSA-N 4-(3-methoxyphenyl)aniline Chemical compound COC1=CC=CC(C=2C=CC(N)=CC=2)=C1 OSWFIVFLDKOXQC-UHFFFAOYSA-N 0.000 abstract description 2
- 235000019253 formic acid Nutrition 0.000 abstract description 2
- 150000003839 salts Chemical class 0.000 abstract 2
- 238000001694 spray drying Methods 0.000 abstract 2
- 239000002253 acid Substances 0.000 abstract 1
- 239000011260 aqueous acid Substances 0.000 abstract 1
- 238000000034 method Methods 0.000 description 13
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 6
- 239000008187 granular material Substances 0.000 description 6
- 230000007935 neutral effect Effects 0.000 description 6
- 239000000243 solution Substances 0.000 description 5
- 238000003756 stirring Methods 0.000 description 4
- 239000003929 acidic solution Substances 0.000 description 3
- 238000004587 chromatography analysis Methods 0.000 description 3
- 230000000052 comparative effect Effects 0.000 description 3
- 239000006185 dispersion Substances 0.000 description 3
- 239000007788 liquid Substances 0.000 description 3
- 235000011121 sodium hydroxide Nutrition 0.000 description 3
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 2
- 241000238557 Decapoda Species 0.000 description 2
- PIICEJLVQHRZGT-UHFFFAOYSA-N Ethylenediamine Chemical compound NCCN PIICEJLVQHRZGT-UHFFFAOYSA-N 0.000 description 2
- 230000021736 acetylation Effects 0.000 description 2
- 239000013543 active substance Substances 0.000 description 2
- 239000000969 carrier Substances 0.000 description 2
- 238000006243 chemical reaction Methods 0.000 description 2
- 230000006196 deacetylation Effects 0.000 description 2
- 238000003381 deacetylation reaction Methods 0.000 description 2
- 239000000839 emulsion Substances 0.000 description 2
- 239000000945 filler Substances 0.000 description 2
- 239000000463 material Substances 0.000 description 2
- 239000000725 suspension Substances 0.000 description 2
- 241000238424 Crustacea Species 0.000 description 1
- 102000004190 Enzymes Human genes 0.000 description 1
- 108090000790 Enzymes Proteins 0.000 description 1
- 241000270295 Serpentes Species 0.000 description 1
- 239000000654 additive Substances 0.000 description 1
- 125000003158 alcohol group Chemical group 0.000 description 1
- 239000012752 auxiliary agent Substances 0.000 description 1
- 239000003518 caustics Substances 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 238000007872 degassing Methods 0.000 description 1
- 238000007599 discharging Methods 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 239000003995 emulsifying agent Substances 0.000 description 1
- 239000010419 fine particle Substances 0.000 description 1
- 239000012530 fluid Substances 0.000 description 1
- 230000008014 freezing Effects 0.000 description 1
- 238000007710 freezing Methods 0.000 description 1
- 230000002209 hydrophobic effect Effects 0.000 description 1
- 230000001788 irregular Effects 0.000 description 1
- 238000010299 mechanically pulverizing process Methods 0.000 description 1
- 238000006386 neutralization reaction Methods 0.000 description 1
- 229910052757 nitrogen Inorganic materials 0.000 description 1
- 239000003960 organic solvent Substances 0.000 description 1
- 238000012856 packing Methods 0.000 description 1
- 239000000546 pharmaceutical excipient Substances 0.000 description 1
- 239000011148 porous material Substances 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- 239000000047 product Substances 0.000 description 1
- 102000004169 proteins and genes Human genes 0.000 description 1
- 108090000623 proteins and genes Proteins 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
- 239000007921 spray Substances 0.000 description 1
- 239000006228 supernatant Substances 0.000 description 1
- 238000001291 vacuum drying Methods 0.000 description 1
Landscapes
- Medicinal Preparation (AREA)
- Polysaccharides And Polysaccharide Derivatives (AREA)
- Treatment Of Liquids With Adsorbents In General (AREA)
- Processes Of Treating Macromolecular Substances (AREA)
Abstract
Description
【産業上の利用分野１
本発明は、クロマトグラフィー用充填材、固定化生理活
性物質用担体、及び医薬用助剤等に好適な多孔質超微小
粒状体の製造方法に関するものである。
【従来の技術】
キチンは海老、蟹等の甲殻類の外皮他自然界に広く分布
して存在し、該キチン及びキチンより得られるキトサン
は、クロマトグラフィー用充填材。
各種物質用担体として用いることができる。キチン及び
キトサンの超微小粒状体を得る方法としては種々の試み
がなされており、超微小粒状キトサンを得る方法として
、キトサンフレークを機械的に粉砕する方法、特公昭５
９−３０７２２号公報に開示されたキトサンの酸性水溶
液に乳化剤を含む疎水性溶剤を入れ、攪拌してエマルジ
ョン化し、このものをアルカリ水溶液中で攪拌しながら
凝固析出する方法が知られているが、何れも形状が不規
則。
若しくは粒径の分布が広い範囲に分布したものとなる等
の欠点がある。又、キチンの超微小球状物を得る方法と
しては特開昭５１１２７７３６号公報及び特開昭５９−
８６６４０号公報に記載のようにキチンを機械的に粉砕
する方法が知られているが、このようにして得られたキ
チンは不規則な形態の粒子であり、分散性に欠けるもの
であった。
Ｋ発明が解決しようとする問題点】
本発明者等は、キトサンを酸性水溶液中に溶解して得た
溶解液を塩基性溶液中で凝固再生し、生成した凝固物を
水中に粉砕分散せしめ、該分散液を高温雰囲気中に加圧
空気と共に吐出乾燥する超微小球状キトサンの製造方法
を発明し、特願昭６０−２０３００６号として出″願を
行った。また、超微小球状キチンの製造方法として、上
記のようにして凝固再生したキトサンを更にアセチル化
して得た再生キチン等の再生キチンを水中に粉砕分散せ
しめ、該分散液を高温雰囲気中に吐出乾燥する方法を発
明し、特願昭６０−２４０８９６号として出願を行った
。
これらの方法により、一旦再生したキトサン又はキチン
を水中に分散せしめて該分散液を高温雰囲気中に吐出乾
燥する方法によると、平均粒径が２０μｍ以下であって
、しかも粒度分布の小さな超微小球状キトサン又はキチ
ンを得ることができる。
しかしながら得られた超微小球状キトサン又はキチンは
比表面積が小さく、例えば酵素、蛋白質等の固定化担体
としては、その固定化量が少なくなり、その結果バイオ
リアクターとしての活性が低いという欠点がある。
本発明は、このような欠点をなくし、平均粒子径が２０
μｍ以下であって、しかも比表面積の大きいキトサン又
はキチンの多孔質超微小粒状体の製造方法を提供するこ
とを目的とする。
Ｋ問題点を解決するための手段】
本発明の方法は、キトサンを酸性水溶液中に溶解し、該
酸性水溶液を高温雰囲気中に噴霧し、乾燥させることに
より超微小粒状キトサン酸塩を得、該超微小粒状キトサ
ン酸塩を塩基性溶液中で中和し、更に中性になるまで充
分に水洗することによって多孔質超微小粒状キトサンを
得るものである。
また、上記のようにして塩基性溶液中で中和し、中性に
なるまで充分に水洗した多孔質超微小粒状キトサンを、
アルコールで水置換後、有機溶媒中でアセチル化試薬と
接触反応させて再度アルコールで洗浄後水洗すれば多孔
質超微小粒状キチンを製造することができる。
本発明方法において用いるキトサンは、通常フレーク状
のものを使用し、平均分子ｉｔ ｉｏ、 ｏｏｏ〜２３
０、０００の低分子量キトサンを使用すると、添加剤等
を加えずに高濃度の酸性水溶液が得られるので好ましい
。キトサンは、酢酸、ジクロール酢酸。
蟻酸の単独、若しくは混合物の水溶液に溶解する。
キトサン酸性水溶液の濃度は１〜２０％が好ましい。
キトサン酸性水溶液は高温雰囲気中に噴霧し、乾燥され
る。高温雰囲気中の温度は、超微小粒状キトサンが乾燥
されるに充分な温度で、１００〜２００℃の範囲で自由
に選択できる。得られる粒状物の粒径は、高温雰囲気中
に噴霧する際、二流体ノズル方式においては吐出量と吐
出圧、ディスク型遠心噴霧法式においては供給量と回転
数を適宜調節することによって、任意に選択することが
できる。乾燥凝固した超微小キトサン′＃！ｉ塩は塩基
性溶液中で中和して多孔質の超微小粒状キトサンを再生
する。中和を行う塩基性溶液の組成は、苛性ソーダ、エ
チレンジアミン、水酸化カリウム等の塩基性物質にメタ
ノール、エタノール、ジメチルホルムアミド等の極性を
有する有機溶媒を添加して調製する。該塩基性溶液は、
水を加えずに調製する。水を加えるとキトサン粒状体が
膨潤し、互いに粘着、凝集をしてしまう。このようにし
て得た多孔質超微小粒状キトサンは、水で中性になるま
で充分洗浄する。
また、多孔質超微小粒状キチンを得るには、上記のよう
にして冑られた多孔質超微小粒状キトサンを、水洗後ア
ルコールで水置換し、例えばエタノール中で無水酢酸を
用いて反応させ、Ｎ−アセチル化を行って再生キチンを
侍る。冑られた多孔質超微小粒状キチンはアルコールで
洗浄後、水洗する。
このようにして得られた本発明のキトサン又はキチン多
孔質超微小粒状体は、平均粒径が２０μｍ以下であって
、しかも粒度分布の小さい多孔性の粒状体である。
Ｋ実 施 例】
実施例１
脱アセチル化度９５％、平均分子量４２ 、０００のキ
トサン７０ｇを、３５ｇの酢酸を含む水９３０ｇに溶解
して、キトサン酸性溶液を得た。この溶液の２０℃にお
ける粘度は、回転粘度計で測定したところ２３００ｃｐ
であった。このキトサン酸性溶液を４ 、０Ｋｆｉ ／
ｃｔｄの加圧空気と共に１７．６ｄ／分の液量で、１
８０〜１８５℃の高温雰囲気中に噴霧して乾燥し、乾燥
物６４ｇをサイクロンコレクターに捕集した。この凝固
物１ｇを、エチレンジアミン１０％、エタノール９０％
からなる塩基性溶液２０ｒｎ！！中で、室温で６０分間
中和した後、これをトミー精Ｉ＃ＲＤ−２０１’％＋型
遠心分離機を用いて、１５００ｒｐｎで１０分ｌｉ！ｌ
遠心し、上澄み液を除去した。これに水２０ｄを加えて
、同じ操作を中性になるまで繰り返し、超微小粒状多孔
質キトサン０．７ｇを得た。これを走査型電子顕微鏡で
調べたところ、平均粒径１０μｍ２粒径分布３〜２０μ
７７Ｌであった。又、比表面積は ７８．０ＴＩｔ、／
ｇであった。比表面積は、試料を液体窒素中で急冷凍結
し、１０−４トール（Ｔｏｒｒ） 、−４０℃、８時間
真空乾燥し、１４０℃、４０分間脱ガス後比表面自動測
定装置（島津マイクロメリテックス２２０形）にてＢＥ
Ｔ法で測定した。
実施例２
脱アセチル化度８２％、平均分子ｍ ｓａ、 ｏｏｏの
キトサン５５ｇに、ジクロル酢酸を含む水９５０ｇを加
えて溶解し、キトサン酸性溶液を待だ。この溶液の２０
℃における粘度は、回転粘度計で測定したところ５００
０ｃｐであった。このキトサン酸性溶液を１８０〜１９
０℃の高温雰囲気中に、回転数２９０００ｒｐｍのディ
スクよりフィードｆｆ１１７ｄ／分で遠心噴霧し、乾燥
微小粒状体４７９を、サイクロンコレクターで捕集した
。この粒状体１ｇを、５０戒の遠沈管に入れ、水酸化カ
リウム１０％及びメタノール９０％からなる塩基性溶液
２０威を加え、室温で６０分分間上うして中和した後、
中性になるまで充分水洗して、超微小粒状多孔質キトサ
ン０゜６ｇを得た。これを走査型電子顕微鏡で調べたと
ころ、平均粒径１５μｍ。
粒径分布５〜３０μ汎であった。又比表面積は２７．４
ＴＩｔ／ｇであった。
実施例３
実施例１と同様にして得た超微小粒状多孔質キトサン１
ｇを、５０ｄの遠沈管に入れ、エタノールで四回置換（
水をアルコールに置換）した後、二倍モルの無水酢酸を
用いて常温で２４時間反応させた。無水酢酸による反応
を五目繰り返した後、エタノールで洗浄水洗し、０．５
Ｎ苛性ソーダでエステル結合切断の為、室温で１時間反
応させ水洗して超微小粒状多孔質キチン０．６ｇを得た
。これを走査型電子顕微鏡で調べたところ、平均粒径８
μｍ９粒径分布３〜１８μｍであった。又、比表面積は
７２．６ＴＩｔ、／ｇであった。
比較例１
実施例１と同様にして侍だキトサン酸性溶液を、１０％
苛性ンーダと３０％メチルアルコール、及び水６０％か
らなる塩基性水溶液中に、孔径０゜２５履のノズルより
落下させて、キトサンを凝固再生し、−〇 −
中性になるまで十分水洗して、粒径０．７〜２．ｏｍｍ
の粒状物を得た。該粒状物６００ｄをとり、日本精機■
製ＡＭ・ ３型ホモジナイザーを用いて、１５０００ｒ
ｐｉｎの回転数で７分間攪拌して、乳状の懸濁液とし、
更に水を加えて全量を１ｏｏｏｉとした。これを攪拌し
ながら分散状態を保ちつつ、３．Ｏｈ／ｃｉの加圧空気
と共に、毎分１７．６７の液量で、１８０℃の高温雰囲
気中に噴霧して乾燥し、平均粒径１０μｍの微小粒状キ
トサン３５ｇを得た。これの比表面積は１．２ＴＩｔ／
ｇであった。
比較例２
比較例１で得た粒径０．７〜２．０．、の粒状物４００
蛇を、４００ｄのエタノールで４回攪拌（水をアルコー
ルに置換）したのち、３＠モルの無水酢酸を用いて常温
で２４ＦＲ間反応させた。この操作を３回繰り返した後
、エタノールで洗浄、水洗し、０．５Ｎ苛性ソーダでエ
ステル結合切断のため室温で１時間反応させて水洗した
。該再生キチン２００ｄに水１００威を加えてホモジナ
イザーで１７０００ｒｐｎ４分間攪拌し、更に水を加え
て４００−とし、濃度３．５％の懸濁液とした。これを
１４．５ｍ！／ｌ１ｉｎ、の吐出量で、４ Ｋｆｌ ／
ｃｄ！の加圧空気とともに、１８０℃の高温雰囲気中
に噴霧し乾燥して、平均粒径３μｍの微小粒状キチン１
１．２ｇを得た。これの比表面積は、１．０ＴＩｔ／ｇ
であった。[Industrial Application Field 1] The present invention relates to a method for producing porous ultrafine particles suitable for use as fillers for chromatography, carriers for immobilized physiologically active substances, pharmaceutical aids, and the like. [Prior Art] Chitin is widely distributed in nature, including the outer skin of crustaceans such as shrimp and crabs, and chitin and chitosan obtained from chitin are used as fillers for chromatography. It can be used as a carrier for various substances. Various attempts have been made to obtain ultrafine granules of chitin and chitosan, including a method of mechanically crushing chitosan flakes, and a method of mechanically crushing chitosan flakes.
A known method is disclosed in Japanese Patent Publication No. 9-30722, in which a hydrophobic solvent containing an emulsifier is added to an acidic aqueous solution of chitosan, the mixture is stirred to form an emulsion, and the emulsion is coagulated and precipitated in an alkaline aqueous solution while being stirred. Both are irregular in shape. Alternatively, there are drawbacks such as the particle size distribution being distributed over a wide range. In addition, as a method for obtaining ultrafine chitin spherules, Japanese Patent Application Laid-Open No. 51127736 and Japanese Patent Application Laid-open No. 59-
Although a method of mechanically pulverizing chitin is known as described in Japanese Patent No. 86640, the chitin thus obtained is irregularly shaped particles and lacks dispersibility. Problems to be Solved by the Invention] The present inventors coagulated and regenerated a solution obtained by dissolving chitosan in an acidic aqueous solution in a basic solution, pulverized and dispersed the resulting coagulate in water, He invented a method for producing ultrafine spherical chitosan by discharging and drying the dispersion liquid together with pressurized air into a high-temperature atmosphere, and filed the application as Japanese Patent Application No. 60-203006. As a production method, we invented a method in which regenerated chitin, such as regenerated chitin obtained by further acetylating the coagulated and regenerated chitosan as described above, is pulverized and dispersed in water, and the dispersion is discharged and dried in a high-temperature atmosphere. The application was filed as Application No. 60-240896. According to these methods, once regenerated chitosan or chitin is dispersed in water and the dispersion is discharged and dried in a high temperature atmosphere, the average particle size is 20 μm or less. Moreover, it is possible to obtain ultrafine spherical chitosan or chitin with a small particle size distribution. However, the obtained ultrafine spherical chitosan or chitin has a small specific surface area and is not suitable as an immobilization carrier for enzymes, proteins, etc. , the amount of immobilized particles is small, and as a result, the activity as a bioreactor is low.The present invention eliminates such drawbacks,
It is an object of the present invention to provide a method for producing porous ultrafine particles of chitosan or chitin having a specific surface area of .mu.m or less and a large specific surface area. Means for Solving Problem K] The method of the present invention involves dissolving chitosan in an acidic aqueous solution, spraying the acidic aqueous solution into a high-temperature atmosphere, and drying it to obtain ultrafine particulate chitosanate; Porous ultrafine chitosan is obtained by neutralizing the ultrafine chitosanate in a basic solution and washing thoroughly with water until it becomes neutral. In addition, porous ultrafine granular chitosan was neutralized in a basic solution as described above and thoroughly washed with water until it became neutral.
After replacing water with alcohol, a contact reaction with an acetylation reagent is carried out in an organic solvent, and the porous ultrafine granular chitin can be produced by washing again with alcohol and then with water. The chitosan used in the method of the present invention is usually in the form of flakes, and has an average molecular weight of it io, ooo ~ 23
It is preferable to use chitosan with a low molecular weight of 0,000 because a highly concentrated acidic aqueous solution can be obtained without adding any additives. Chitosan is acetic acid and dichloroacetic acid. Dissolves in an aqueous solution of formic acid alone or as a mixture. The concentration of the chitosan acidic aqueous solution is preferably 1 to 20%. The chitosan acidic aqueous solution is sprayed into a high temperature atmosphere and dried. The temperature in the high temperature atmosphere is a temperature sufficient to dry the ultrafine chitosan particles, and can be freely selected within the range of 100 to 200°C. When spraying into a high-temperature atmosphere, the particle size of the resulting granules can be adjusted arbitrarily by appropriately adjusting the discharge amount and discharge pressure in the two-fluid nozzle method, and the supply amount and rotation speed in the disk-type centrifugal spray method. You can choose. Dry and solidified ultra-fine chitosan'#! The i-salt is neutralized in a basic solution to regenerate porous ultrafine chitosan particles. The composition of the basic solution for neutralization is prepared by adding a polar organic solvent such as methanol, ethanol, dimethylformamide, etc. to a basic substance such as caustic soda, ethylenediamine, or potassium hydroxide. The basic solution is
Prepare without adding water. When water is added, the chitosan particles swell, causing them to stick to each other and coagulate. The porous ultrafine particulate chitosan thus obtained is thoroughly washed with water until it becomes neutral. In order to obtain porous ultrafine chitin, the porous ultrafine chitosan removed as described above is washed with water, replaced with alcohol, and reacted with acetic anhydride in ethanol, for example. , performs N-acetylation to prepare regenerated chitin. The porous ultrafine granular chitin that has been removed is washed with alcohol and then with water. The chitosan or chitin porous ultrafine particles of the present invention thus obtained are porous particles with an average particle size of 20 μm or less and a narrow particle size distribution. K Examples Example 1 70 g of chitosan having a degree of deacetylation of 95% and an average molecular weight of 42,000 was dissolved in 930 g of water containing 35 g of acetic acid to obtain an acidic chitosan solution. The viscosity of this solution at 20°C was 2300 cp as measured by a rotational viscometer.
Met. This chitosan acidic solution was added at 4,0Kfi/
1 at a flow rate of 17.6 d/min with pressurized air at ctd.
It was dried by spraying in a high temperature atmosphere of 80 to 185°C, and 64 g of the dried product was collected in a cyclone collector. 1 g of this coagulated material was mixed with 10% ethylenediamine and 90% ethanol.
A basic solution consisting of 20rn! ! After neutralizing for 60 minutes at room temperature, the mixture was stirred at 1500 rpm for 10 minutes using a Tommy Sei I#RD-201'%+ type centrifuge. l
It was centrifuged and the supernatant was removed. 20 d of water was added to this, and the same operation was repeated until the mixture became neutral, to obtain 0.7 g of ultrafine porous chitosan particles. When this was examined using a scanning electron microscope, the average particle size was 10 μm2, and the particle size distribution was 3 to 20 μm.
It was 77L. Also, the specific surface area is 78.0TIt, /
It was g. The specific surface area was determined by rapidly freezing the sample in liquid nitrogen, vacuum drying at 10-4 Torr at -40°C for 8 hours, and degassing at 140°C for 40 minutes using an automatic specific surface measuring device (Shimadzu Micromeritex). 220 type) BE
Measured by T method. Example 2 950 g of water containing dichloroacetic acid was added to 55 g of chitosan with a degree of deacetylation of 82% and an average molecular weight of m sa ooo, and dissolved, and an acidic chitosan solution was prepared. 20 of this solution
The viscosity at °C was 500 when measured with a rotational viscometer.
It was 0 cp. Add this chitosan acidic solution to 180-19
In a high-temperature atmosphere at 0° C., centrifugal spraying was performed from a disk at a rotational speed of 29,000 rpm at a feed rate of 117 d/min, and dried fine particles 479 were collected with a cyclone collector. 1 g of this granular material was placed in a 50% centrifuge tube, 20% of a basic solution consisting of 10% potassium hydroxide and 90% methanol was added, and the mixture was neutralized by stirring at room temperature for 60 minutes.
The mixture was thoroughly washed with water until it became neutral, and 0.6 g of ultrafine porous chitosan particles were obtained. When this was examined using a scanning electron microscope, the average particle size was 15 μm. The particle size distribution ranged from 5 to 30μ. Also, the specific surface area is 27.4
It was TIt/g. Example 3 Ultrafine granular porous chitosan 1 obtained in the same manner as Example 1
g was placed in a 50d centrifuge tube and replaced with ethanol four times (
After replacing water with alcohol), the mixture was reacted with twice the molar amount of acetic anhydride at room temperature for 24 hours. After repeating the reaction with acetic anhydride five times, washing with ethanol and water,
In order to cleave the ester bonds with N caustic soda, the mixture was reacted at room temperature for 1 hour and washed with water to obtain 0.6 g of ultrafine porous chitin particles. When this was examined using a scanning electron microscope, the average particle size was 8.
μm9 particle size distribution was 3 to 18 μm. Further, the specific surface area was 72.6 TIt,/g. Comparative Example 1 A 10% Samurai chitosan acidic solution was prepared in the same manner as in Example 1.
Chitosan is solidified and regenerated by dropping it into a basic aqueous solution consisting of caustic powder, 30% methyl alcohol, and 60% water through a nozzle with a pore size of 0.25 mm, and then thoroughly washed with water until it becomes neutral. , particle size 0.7-2. omm
granules were obtained. Take 600 d of the granules and use Nippon Seiki ■
15000 r using AM・3 type homogenizer made by
Stir at pin speed for 7 minutes to make a milky suspension,
Further water was added to bring the total amount to 1 oooi. While stirring this to maintain a dispersed state, 3. The mixture was sprayed and dried in a high-temperature atmosphere at 180° C. at a liquid rate of 17.67 per minute together with pressurized air of Oh/ci to obtain 35 g of microparticulate chitosan with an average particle size of 10 μm. The specific surface area of this is 1.2TIt/
It was g. Comparative Example 2 The particle size obtained in Comparative Example 1 was 0.7 to 2.0. , granules of 400
After stirring the snake four times with 400 d of ethanol (replacing water with alcohol), it was reacted with 3@mol acetic anhydride at room temperature for 24 FR. After repeating this operation three times, it was washed with ethanol and water, reacted with 0.5N caustic soda at room temperature for 1 hour to cleave the ester bond, and washed with water. 100 parts of water was added to 200 d of the regenerated chitin, stirred for 4 minutes at 17,000 rpm using a homogenizer, and water was further added to make 400 parts of the chitin to obtain a suspension with a concentration of 3.5%. This is 14.5m! /l1in, with a discharge rate of 4 Kfl/
CD! It is sprayed with pressurized air in a high temperature atmosphere of 180°C and dried to produce microparticulate chitin 1 with an average particle size of 3 μm.
1.2g was obtained. The specific surface area of this is 1.0TIt/g
Met.
本発明によるキトサン又はキチン多孔質超微小粒状体は
、キトサン酸性水溶液から超微小粒状キトサン酸塩を得
、このものを塩基性溶液中で中和することによって多孔
質の超微小粒状キトサンを再生せしめ、必要に応じて、
更にアセチル化を行えば、多孔質の超微小粒状キチンが
得られるものである。
従って、実施例にも記載のように、本発明の方法によっ
て得られたキトサン又はキチン多孔質超微小粒状体は、
平均粒子径が２０μ而以下という超微小粒子で、粒径分
布の小さい粒度の揃ったものであり、しかも比表面積が
極めて大きいので、クロマトグラフィー用充填材、固定
化生理活性物質用担体、医薬用助剤等に極めて好適なも
のである。The porous ultrafine particles of chitosan or chitin according to the present invention are obtained by obtaining ultrafine particulate chitosanate from an acidic chitosan aqueous solution and neutralizing this in a basic solution. and if necessary,
If acetylation is further performed, porous ultrafine chitin particles can be obtained. Therefore, as described in the Examples, the chitosan or chitin porous ultrafine particles obtained by the method of the present invention are
Ultra-fine particles with an average particle size of 20μ or less, uniform particle size with a small particle size distribution, and an extremely large specific surface area, so they can be used as packing materials for chromatography, carriers for immobilized physiologically active substances, and pharmaceuticals. It is extremely suitable for use as an auxiliary agent.
Claims (1)
させた後、塩基性溶液中で中和させることを特徴とする
多孔質超微小粒状体の製造方法。 ２、キトサン酸性水溶液を高温雰囲気中に噴霧して乾燥
させた後、塩基性溶液中で中和させ、次いでアセチル化
することを特徴とする多孔質超微小粒状体の製造方法。 ３、該塩基性溶液が、塩基性物質を極性を有する有機溶
媒中に添加してものである特許請求の範囲第１項又は第
２項に記載の多孔質超微小粒状体の製造方法。 ４、極性を有する有機溶媒が、メタノール、エタノール
、ジメチルホルムアミドの何れか、又はこれらの混合物
からなる特許請求の範囲第３項に記載の多孔質超微小粒
状体の製造方法。[Claims] 1. A method for producing porous ultrafine particles, which comprises spraying an acidic chitosan aqueous solution into a high-temperature atmosphere, drying it, and then neutralizing it in a basic solution. 2. A method for producing porous ultrafine particles, which comprises spraying an acidic chitosan aqueous solution into a high-temperature atmosphere, drying it, neutralizing it in a basic solution, and then acetylating it. 3. The method for producing porous ultrafine particles according to claim 1 or 2, wherein the basic solution is obtained by adding a basic substance to a polar organic solvent. 4. The method for producing porous ultrafine particles according to claim 3, wherein the polar organic solvent comprises methanol, ethanol, dimethylformamide, or a mixture thereof.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP62043998A JPS63210101A (en) | 1987-02-26 | 1987-02-26 | Manufacture of ultrafine porous chitosan or chitin particle |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP62043998A JPS63210101A (en) | 1987-02-26 | 1987-02-26 | Manufacture of ultrafine porous chitosan or chitin particle |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JPS63210101A true JPS63210101A (en) | 1988-08-31 |
| JPH0212961B2 JPH0212961B2 (en) | 1990-04-03 |
Family
ID=12679382
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP62043998A Granted JPS63210101A (en) | 1987-02-26 | 1987-02-26 | Manufacture of ultrafine porous chitosan or chitin particle |
Country Status (1)
| Country | Link |
|---|---|
| JP (1) | JPS63210101A (en) |
Cited By (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2000061109A1 (en) * | 1999-04-12 | 2000-10-19 | Shionogi & Co., Ltd. | Process for producing medicinal composition of basic hydrophobic medicinal compound |
| US6252003B1 (en) | 1998-06-04 | 2001-06-26 | Kao Corporation | Polymer emulsion and process for producing the same |
| KR100470715B1 (en) * | 2002-04-04 | 2005-03-08 | 주식회사 자광 | A capsule of porous bead of water soluble chitosan and the preparation method thereof |
| KR100486042B1 (en) * | 2002-04-18 | 2005-04-29 | 강대인 | Method for preparing chitin hydrolysates having low molecular weight and oligosaccharides by the enzyme treatment |
| KR20050055643A (en) * | 2005-04-25 | 2005-06-13 | 조석형 | Diet agent containing chitosan microparticle and the preparation method thereof |
| CN102352047A (en) * | 2011-06-27 | 2012-02-15 | 张会艳 | Preparation method of chitin balls |
| WO2024095351A1 (en) * | 2022-10-31 | 2024-05-10 | 綜研化学株式会社 | Precursor polysaccharide-containing particles, polysaccharide-containing particles, and method for producing polysaccharide-containing particles |
-
1987
- 1987-02-26 JP JP62043998A patent/JPS63210101A/en active Granted
Cited By (10)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US6252003B1 (en) | 1998-06-04 | 2001-06-26 | Kao Corporation | Polymer emulsion and process for producing the same |
| US6359032B1 (en) | 1998-06-04 | 2002-03-19 | Kao Corporation | Polymer emulsion and process for preparing the same |
| WO2000061109A1 (en) * | 1999-04-12 | 2000-10-19 | Shionogi & Co., Ltd. | Process for producing medicinal composition of basic hydrophobic medicinal compound |
| US6858230B1 (en) | 1999-04-12 | 2005-02-22 | Shionogi & Co., Ltd. | Process for producing medicinal composition of basic hydrophobic medicinal compound |
| KR100470715B1 (en) * | 2002-04-04 | 2005-03-08 | 주식회사 자광 | A capsule of porous bead of water soluble chitosan and the preparation method thereof |
| KR100486042B1 (en) * | 2002-04-18 | 2005-04-29 | 강대인 | Method for preparing chitin hydrolysates having low molecular weight and oligosaccharides by the enzyme treatment |
| KR20050055643A (en) * | 2005-04-25 | 2005-06-13 | 조석형 | Diet agent containing chitosan microparticle and the preparation method thereof |
| CN102352047A (en) * | 2011-06-27 | 2012-02-15 | 张会艳 | Preparation method of chitin balls |
| WO2024095351A1 (en) * | 2022-10-31 | 2024-05-10 | 綜研化学株式会社 | Precursor polysaccharide-containing particles, polysaccharide-containing particles, and method for producing polysaccharide-containing particles |
| WO2024096016A1 (en) * | 2022-10-31 | 2024-05-10 | 綜研化学株式会社 | Polysaccharide-containing particle production method, precursor polysaccharide-containing particles, and polysaccharide-containing particles |
Also Published As
| Publication number | Publication date |
|---|---|
| JPH0212961B2 (en) | 1990-04-03 |
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